The aim of this program is to demonstrate the applicability and development of new synthetic principles and reactions to problems in organic chemistry related to chemotherapeutically important compounds. The new routes developed will lead to practical approaches to macrocycles, prostanoids, steroids, Beta-lactam antibiotics, and related systems. The use of transition metal templates as the "chemist's enzymes" to exercise chemoselectivity, regioselectivity, and stereocontrol in an absolute and relative sense constitutes a major aspect of this proposal. Macrolides include the broad spectrum antibiotics related to the erythromycins and the polyene antifungal compounds of the amphotericin type. An all carbon macrocycle that possesses antitumor activity is represented by aspochalasin. Chiral synthesis and creation of stereochemistry in conformationally non-rigid systems (ie. acyclic ones) represent major aspects of the proposed strategies to prostanoids (of broad clinical application) and Vitamin D metabolites, of potential use in osteoporosis. New bond forming reactions will also address problems in picrotoxins, neurotransmitter inhibitors, and broad spectrum Beta-lactam antibiotics.